A Global SU(5) F-theory model with Wilson line breaking

We engineer compact SU(5) Grand Unified Theories in F-theory in which GUT-breaking is achieved by a discrete Wilson line. Because the internal gauge field is flat, these models avoid the high scale threshold corrections associated with hypercharge flux. Along the way, we exemplify the `local-to-global' approach in F-theory model building and demonstrate how the Tate divisor formalism can be used to address several challenges of extending local models to global ones. These include in particular the construction of G-fluxes that extend non-inherited bundles and the engineering of U(1) symmetries. We go beyond chirality computations and determine the precise (charged) massless spectrum, finding exactly three families of quarks and leptons but excessive doublet and/or triplet pairs in the Higgs sector (depending on the example) and vector-like exotics descending from the adjoint of SU(5)_{GUT}. Understanding why vector-like pairs persist in the Higgs sector without an obvious symmetry to protect them may shed light on new solutions to the mu problem in F-theory GUTs.Comment: 95 pages (71 pages + 1 Appendix); v2 references added, minor correction

Congenital Plasmodium vivax malaria mimicking neonatal sepsis: a case report

Although malaria in pregnancy can cause very significant neonatal morbidity, congenital malaria is a very rare condition in both endemic and non-endemic areas. A case of congenital malaria by Plasmodium vivax, initially mistaken for neonatal sepsis, is described. The correct diagnosis was accidentally done, as congenital malaria had been missed in the initial differential diagnosis

Genome-Wide Comparative Gene Family Classification

Correct classification of genes into gene families is important for understanding gene function and evolution. Although gene families of many species have been resolved both computationally and experimentally with high accuracy, gene family classification in most newly sequenced genomes has not been done with the same high standard. This project has been designed to develop a strategy to effectively and accurately classify gene families across genomes. We first examine and compare the performance of computer programs developed for automated gene family classification. We demonstrate that some programs, including the hierarchical average-linkage clustering algorithm MC-UPGMA and the popular Markov clustering algorithm TRIBE-MCL, can reconstruct manual curation of gene families accurately. However, their performance is highly sensitive to parameter setting, i.e. different gene families require different program parameters for correct resolution. To circumvent the problem of parameterization, we have developed a comparative strategy for gene family classification. This strategy takes advantage of existing curated gene families of reference species to find suitable parameters for classifying genes in related genomes. To demonstrate the effectiveness of this novel strategy, we use TRIBE-MCL to classify chemosensory and ABC transporter gene families in C. elegans and its four sister species. We conclude that fully automated programs can establish biologically accurate gene families if parameterized accordingly. Comparative gene family classification finds optimal parameters automatically, thus allowing rapid insights into gene families of newly sequenced species

Do Doctors Vote?

BACKGROUND: Organizational leaders and scholars have issued calls for the medical profession to refocus its efforts on fulfilling the core tenets of professionalism. A key element of professionalism is participation in community affairs. OBJECTIVE: To measure physician voting rates as an indicator of civic participation. DESIGN: Cross-sectional survey of a subgroup of physicians from a nationally representative household survey of civilian, noninstitutionalized adult citizens. PARTICIPANTS: A total of 350,870 participants in the Current Population Survey (CPS) November Voter Supplement from 1996–2002, including 1,274 physicians and 1,886 lawyers; 414,989 participants in the CPS survey from 1976–1982, including 2,033 health professionals. MEASUREMENTS: Multivariate logistic regression models were used to compare adjusted physician voting rates in the 1996–2002 congressional and presidential elections with those of lawyers and the general population and to compare voting rates of health professionals in 1996–2002 with those in 1976–1992. RESULTS: After multivariate adjustment for characteristics known to be associated with voting rates, physicians were less likely to vote than the general population in 1998 (odds ratio 0.76; 95% confidence interval [CI] 0.59–0.99), 2000 (odds ratio 0.64; 95% CI 0.44–0.93), and 2002 (odds ratio 0.62; 95% CI 0.48–0.80) but not 1996 (odds ratio 0.83; 95% CI 0.59–1.17). Lawyers voted at higher rates than the general population and doctors in all four elections (P < .001). The pooled adjusted odds ratio for physician voting across the four elections was 0.70 (CI 0.61–0.81). No substantial changes in voting rates for health professionals were observed between 1976–1982 and 1996–2002. CONCLUSIONS: Physicians have lower adjusted voting rates than lawyers and the general population, suggesting reduced civic participation

Cryopyrin-Associated Periodic Syndrome: An Update on Diagnosis and Treatment Response

Cryopyrin-associated periodic syndrome (CAPS) is a rare hereditary inflammatory disorder encompassing a continuum of three phenotypes: familial cold autoinflammatory syndrome, Muckle-Wells syndrome, and neonatal-onset multisystem inflammatory disease. Distinguishing features include cutaneous, neurological, ophthalmologic, and rheumatologic manifestations. CAPS results from a gain-of-function mutation of the NLRP3 gene coding for cryopyrin, which forms intracellular protein complexes known as inflammasomes. Defects of the inflammasomes lead to overproduction of interleukin-1, resulting in inflammatory symptoms seen in CAPS. Diagnosis is often delayed and requires a thorough review of clinical symptoms. Remarkable advances in our understanding of the genetics and the molecular pathway that is responsible for the clinical phenotype of CAPS has led to the development of effective treatments. It also has become clear that the NLRP3 inflammasome plays a critical role in innate immune defense and therefore has wider implications for other inflammatory disease states

Laser cooling of a nanomechanical oscillator into its quantum ground state

A patterned Si nanobeam is formed which supports co-localized acoustic and optical resonances that are coupled via radiation pressure. Starting from a bath temperature of T=20K, the 3.68GHz nanomechanical mode is cooled into its quantum mechanical ground state utilizing optical radiation pressure. The mechanical mode displacement fluctuations, imprinted on the transmitted cooling laser beam, indicate that a final phonon mode occupancy of 0.85 +-0.04 is obtained.Comment: 18 pages, 10 figure

Fusion of bone-marrow-derived cells with Purkinje neurons, cardiomyocytes and hepatocytes

Recent studies have suggested that bone marrow cells possess a broad differentiation potential, being able to form new liver cells, cardiomyocytes and neurons(1,2). Several groups have attributed this apparent plasticity to 'transdifferentiation'(3-5). Others, however, have suggested that cell fusion could explain these results(6-9). Using a simple method based on Cre/lox recombination to detect cell fusion events, we demonstrate that bone-marrow-derived cells (BMDCs) fuse spontaneously with neural progenitors in vitro. Furthermore, bone marrow transplantation demonstrates that BMDCs fuse in vivo with hepatocytes in liver, Purkinje neurons in the brain and cardiac muscle in the heart, resulting in the formation of multinucleated cells. No evidence of transdifferentiation without fusion was observed in these tissues. These observations provide the first in vivo evidence for cell fusion of BMDCs with neurons and cardiomyocytes, raising the possibility that cell fusion may contribute to the development or maintenance of these key cell types.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62789/1/nature02069.pd

Clinical significance of altered nm23-H1, EGFR, RB and p53 expression in bilharzial bladder cancer

<p>Abstract</p> <p>Background</p> <p>Clinical characterization of bladder carcinomas is still inadequate using the standard clinico-pathological prognostic markers. We assessed the correlation between <it>nm23-H1</it>, <it>Rb, EGFR </it>and <it>p53 </it>in relation to the clinical outcome of patients with muscle invasive bilharzial bladder cancer (MI-BBC).</p> <p>Methods</p> <p><it>nm23-H1</it>, <it>Rb, EGFR and p53 </it>expression was assessed in 59 MI-BBC patients using immunohistochemistry and reverse transcription (RT-PCR) and was correlated to the standard clinico-pathological prognostic factors, patient's outcome and the overall survival (OS) rate.</p> <p>Results</p> <p>Overexpression of <it>EGFR </it>and <it>p53 </it>proteins was detected in 66.1% and 35.6%; respectively. Loss of <it>nm23-H1</it>and <it>Rb </it>proteins was detected in 42.4% and 57.6%; respectively. Increased <it>EGFR and </it>loss of <it>nm23-H1 </it>RNA were detected in 61.5% and 36.5%; respectively. There was a statistically significant correlation between <it>p53 </it>and <it>EGFR </it>overexpression (<it>p </it>< 0.0001), <it>nm23 </it>loss (protein and RNA), lymph node status (<it>p </it>< 0.0001); between the incidence of local recurrence and <it>EGFR </it>RNA overexpression (p= 0.003) as well as between the incidence of metastasis and altered <it>Rb </it>expression (<it>p </it>= 0.026), <it>p53 </it>overexpression (<it>p </it>< 0.0001) and mutation (<it>p </it>= 0.04). Advanced disease stage correlated significantly with increased <it>EGFR </it>(protein and RNA) (<it>p </it>= 0.003 & 0.01), reduced <it>nm23-H1 </it>RNA (<it>p </it>= 0.02), altered <it>Rb </it>(<it>p </it>= 0.023), and <it>p53 </it>overexpression (<it>p </it>= 0.004). OS rates correlated significantly, in univariate analysis, with <it>p53 </it>overexpression (<it>p </it>= 0.011), increased <it>EGFR </it>(protein and RNA, <it>p </it>= 0.034&0.031), <it>nm23-H1 RNA </it>loss (<it>p </it>= 0.021) and aberrations of ≥ 2 genes. However, multivariate analysis showed that only high <it>EGFR </it>overexpression, metastatic recurrence, high tumor grade and the combination of ≥ 2 affected markers were independent prognostic factors.</p> <p>Conclusion</p> <p><it>nm23-H1, EGFR </it>and <it>p53 </it>could be used as prognostic biomarkers in MI-BBC patients. In addition to the standard pathological prognostic factors, a combination of these markers (≥ 2) has synergistic effects in stratifying patients into variable risk groups. The higher is the number of altered biomarkers, the higher will be the risk of disease progression and death.</p

Targeted disruption of Slc2a8 (GLUT8) reduces motility and mitochondrial potential of spermatozoa

GLUT8 is a class 3 sugar transport facilitator which is predominantly expressed in testis and also detected in brain, heart, skeletal muscle, adipose tissue, adrenal gland, and liver. Since its physiological function in these tissues is unknown, we generated a Slc2a8 null mouse and characterized its phenotype. Slc2a8 knockout mice appeared healthy and exhibited normal growth, body weight development and glycemic control, indicating that GLUT8 does not play a significant role for maintenance of whole body glucose homeostasis. However, analysis of the offspring distribution of heterozygous mating indicated a lower number of Slc2a8 knockout offspring (30.5:47.3:22.1%, Slc2a8+/+, Slc2a8+/−, and Slc2a8−/− mice, respectively) resulting in a deviation (p = 0.0024) from the expected Mendelian distribution. This difference was associated with lower ATP levels, a reduced mitochondrial membrane potential and a significant reduction of sperm motility of the Slc2a8 knockout in comparison to wild-type spermatozoa. In contrast, number and survival rate of spermatozoa were not altered. These data indicate that GLUT8 plays an important role in the energy metabolism of sperm cells